Activation of mouse liver natural killer cells and NK1.1+ T cells by bacterial superantigen-primed Kupffer cells
Activation of mouse liver natural killer cells and NK1.1+ T cells by bacterial superantigen-primed Kupffer cells
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DOI：
10.1002/hep.510300209
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发表时间：
1999-08-01
期刊：
影响因子：
13.5
通讯作者：
Sekine, I
中科院分区：
文献类型：
--
作者：
Dobashi, H;Seki, S;Sekine, I
虽然细菌超抗原已被充分表征为T细胞的有效刺激物，但它们在自然杀伤（NK）型细胞中的作用在很大程度上仍然未知。在本研究中，我们研究了细菌超抗原对小鼠肝脏NK细胞和NK 1.1 Ag+（NK 1（+））T细胞的影响。C57 BL/6小鼠静脉注射葡萄球菌肠毒素B（SE B）或链球菌致热外毒素A（SPE-A），注射超抗原后4 h取小鼠各脏器单个核细胞（MNC）培养48 h，测定上清液中IFN-γ水平。给小鼠注射超抗原后24小时，检测小鼠肝、脾MNC的抗肿瘤细胞毒性。肝MNC产生更多的IFN-γ比脾细胞，外周血和肺MNC没有产生任何可检测的IFN-γ。此外，SEE注射后，肝脏MNC获得了强的抗肿瘤细胞毒性，体内或体外细胞耗竭实验表明，NK细胞和NK 1（+）T细胞而不是分化簇（CD）8（+）T细胞负责细胞毒性，NK型细胞部分负责血清IFN-γ的升高，肝脏NK细胞的活化也得到了以下事实的支持：在注射SEE后，肝脏NK细胞成比例地增加，并且NK 1（+）T细胞增加了它们的CD 11 a表达。用抗IFN-γ抗体和/或抗IL-12抗体预处理小鼠可降低肝MNC的细胞毒性。体内去除枯否细胞可降低肝MNC的细胞毒性。与这些结果一致，在体外枯否细胞存在下用超抗原刺激的肝MNC比没有枯否细胞或脾细胞的肝MNC产生更大量的IFN-γ。我们的研究结果表明，细菌超抗原引发的枯否细胞产生IL-12和其他单核细胞因子，同时也非特异性激活NK细胞和NK 1（+）T细胞产生IFN-γ。
Although bacterial superantigens have been well characterized as potent stimulators of T cells, their role in natural killer (NK)-type cells remains largely unknown. In the present study, we examined the effect of bacterial superantigens on mouse liver NK cells and NK1.1 Ag+ (NK1(+)) T cells. C57BL/6 mice were intravenously injected with staphylococcal enterotoxin B (SEB) or streptococcal pyrogenic exotoxin A (SPE-A), and mononuclear cells (MNC) of various organs were obtained from mice 4 hours after bring injected with superantigen, MNC were cultured for 48 hours, and interferon gamma (IFN-gamma) levels of supernatants were measured. The antitumor cytotoxicities of the liver and spleen MNC were also evaluated 24 hours after the mice were injected with superantigen. Liver MNC produced more IFN-gamma than did splenocytes, and peripheral blood and lung MNC did not produce any detectable IFN-gamma. In addition, liver MNC acquired a potent antitumor cytotoxicity by the SEE injection, and both NK cells and NK1(+)T cells but not cluster of differentiation (CD)8(+) T cells were responsible for the cytotoxicity as demonstrated by either in vivo or in vitro cell depletion experiments, and the NK-type cells were partly responsible for the increased serum IFN-gamma, Activation of liver NK-type cells was also supported by the fact that liver NK cells proportionally increased and NK1(+)T cells augmented their CD11a expressions after SEE injection. The pretreatment of mice with anti-IFN-gamma Ab and/or with anti-interleukin-12 (IL-12) Ab diminished the SEE-induced cytotoxicity of liver MNC, Furthermore, the in vivo depletion of Kupffer cells decreased the SEE-induced cytotoxicity of liver MNC. Consistent with these results, liver MNC stimulated with superantigens in the presence of Kupffer cells in vitro produced a greater amount of IFN-gamma than did the liver MNC without Kupffer cells or splenocytes. Our results suggest that bacterial superantigen-primed Kupffer cells produce IL-12 and other monokines, while also nonspecifically activating both NK cells and NK1(+) T cells to produce IFN-gamma.